Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China.
Mol Med. 2024 Sep 28;30(1):167. doi: 10.1186/s10020-024-00933-5.
Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short-term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH.
Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo.
Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses.
Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.
糖皮质激素相关性股骨头坏死（GA-ONFH）是一种进展性骨病，常导致股骨头塌陷和髋关节功能障碍。骨硬化蛋白（SOST）主要由骨细胞分泌，在骨稳态和骨骼完整性的稳态中发挥重要作用。我们之前的研究报告称，短期使用糖皮质激素会增加血清骨硬化蛋白水平。本研究旨在确定骨硬化蛋白是否在 GA-ONFH 的发生和发展中起重要作用。
收集糖皮质激素诱导的股骨头坏死（ARCO Ⅱ期）样本并进行骨硬化蛋白染色。使用成骨细胞系 Ocy454、MC3T3-E1 和内皮细胞。MC3T3-E1 或内皮细胞与 Ocy454 或沉默 SOST 的 Ocy454 在地塞米松存在下共培养，以模拟骨龛中各种细胞的串扰。建立 GA-ONFH 大鼠模型和 SOST 敲除模型，以更好地了解体内现象。
骨硬化蛋白在坏死区的骨坏死患者样本中高度浓缩。与成骨细胞共培养加剧了地塞米松对 MC3T3-E1 和内皮细胞的抑制作用。成骨细胞来源的骨硬化蛋白通过抑制 Wnt 通路损害成骨和血管生成。在 GA-ONFH 大鼠模型中，与野生型组相比，SOST 敲除通过组织学、免疫组织化学和骨代谢分析改善了骨坏死的发生率和改善了骨代谢。
骨硬化蛋白通过损害成骨和血管生成，促进 GA-ONFH 的病理过程。
